1. Field of the Invention
The present invention relates to an aqueous dispersion containing liposomes. More specifically, the present invention relates to an aqueous dispersion containing liposomes containing a hydroxy acid and an amino acid as stabilizing agents.
2. Prior Art
Liposomes are vesicles composed of lipid bilayer membranes and their applications have recently been developed in various fields such as drug delivery systems, diagnostic drugs, artificial enzyme carriers, sensors and cosmetics. In particular, liposomes encapsulating drugs have been actively developed for the purposes of stabilization of unstable drugs, slow release of drugs in living bodies and targeting of drugs to lesion sites. However, liposomes themselves are often unstable to heat and it has been known that, even though they are prepared as a suspension, they relatively rapidly exhibit aggregation or fusion with one another as well as precipitation and coloration. Thus, these problems have been great problems of the commercialization of liposome formulations.
Hitherto, some studies have been conducted to improve the storage stability of liposomes. However, many of them mainly aimed at repressing the aggregation of liposomes, preventing the precipitation of liposomes and preventing the leak of encapsulated materials, and much attention has not been paid to the change of apparent color, i.e., the coloration, which can be very easily recognized upon their practical use. This coloring phenomenon has been known to be caused by the degradation products which are given by the peroxidation degradation of phospholipids generally used as lipids for forming liposomes. As a solution of this problem, there have been proposed liposome formulations where vitamin E is added to the lipids for forming liposomes (Japanese Patent Application Laid-Open (KOKAI) No. 2-295917). However, vitamin E itself is very unstable to heat, light and oxygen and has a problem of giving change of color upon its degradation.
On the other hand, Japanese Patent Application Laid-Open (KOKAI) No. 62-42733 discloses that liposomes were prepared by using dipalmitoylphosphatidylcholine, a synthetic phospholipid, as a lipid for forming liposomes and specific hydrating agents and sterilized by heat and these liposomes were stable without change of color after one year storage at room temperature. However, the stabilizing effect of the hydrating agents on liposomes prepared by using yolk lecithin or soybean lecithin was not described or suggested at all. Moreover, the liposomes composed of synthetic phospholipids have a problem from an economical point of view since they are very expensive even though they are more stable than those composed of natural phospholipids.